The endothelium is the tissue that lines the inner surface of blood vessels, lymphatic vessels and the heart. It is made up of a monolayer of flat, polygonal cells, called endothelial cells or endotheliocytes, which come into direct contact with the blood (or with the lymph) in their apical part; at the base, on the other hand, they are anchored to the basal lamina and through it to the underlying tissues (medium or muscular tunic and adventitious tunic rich in fibrous tissue).
The endothelial cells are very thin and closely linked to each other, so that the endothelial surface does not present any discontinuity (with the exception of the sinusoids); typically, they take on an elongated shape towards the direction of blood flow, especially in the arterial vessels of greater caliber; in the smaller ones (capillaries), they are characterized by extreme thinness, with a thickness that in many cases does not exceed 0.2µm (the muscular and adventitious tunics are also missing at the capillary level).
In general, the endothelium, although similar from a structural point of view, is functionally different depending on the organ in which it is located. The endothelium of the inner surface of the heart is called the endocardium.
Endothelial organ
Considering the endothelial tissue as a simple internal lining of the vessels is very reductive, so much so that today the endothelium is considered a real organ, roughly made up of over a thousand billion cells which together weigh as much as the liver.
The endothelium can be considered an autocrine and paracrine organ as it is capable of secreting, in response to a great variety of signals, numerous chemical mediators that modify the behavior of both the cells that produced them and those nearby. The result is a modulation of vascular tone and blood flow in response to nervous, humoral and mechanical stimuli.
The functions performed by the endothelium are diverse and in some ways complex (and the mediators produced by its cells are even more numerous); let's see the main ones:
- Barrier function: the endothelium is similar to a semi-permeable membrane that controls the passage of substances from the extracellular fluid to the bloodstream and vice versa;
- Regulation of coagulation, fibrinolysis and platelet aggregation; balance of blood fluidity
- Control of leukocyte adhesion and infiltration
- Control of the proliferation of smooth muscle cells of the media tunic; modulation of tone, permeability and vascular structure: plays a very important role in the remodeling observed in hypertension, in re-stenosis after percutaneous coronary intervention and in atherosclerosis
- Formation of new blood vessels (angiogenesis)
- Oxidation of LDL and regulation of inflammatory processes
The chemical mediators produced by the endothelium can be distinguished in vasodilators, which increase the lumen of the vessels and also possess anti-proliferative, anti-thrombotic and anti-atherogenic action, and vasoconstrictors, which instead have the opposite function.
- tissue plasminogen activator (tPA): activates the transformation of plasminogen into plasmin (fibrinolytic enzyme that "dissolves clots - thrombi - of blood").
- glycosaminoglycans (heparin-like): increase the activity of antithrombin III (ATIII), a protein produced by the liver and neutralizing coagulation factors.
- prostacyclin I2 (PGI2): derives from arachidonic acid; causes vasodilation and inhibits platelet adhesion and aggregation; constitutes a reserve system that is activated when the endothelium is damaged and cannot produce high levels of nitric oxide
- thrombomodulin: contributes to the activation of protein C (thrombin cofactor); as such, it is a coagulation inhibitor;
- nitric oxide (see below)
- activation of von Willebrand factor (vWF): binds platelets to collagen and activates platelet aggregation
- release of tissue factor or tissue thromboplastin (TF or FIII): activates factor VII in the extrinsic pathway of coagulation.
- endothelin: induce strong vasoconstriction and proliferation of smooth muscle cells of the vessel wall (tunica media); they increase the vasoconstrictor activity of hormones such as angiotensin II, serotoinin and norepinephrine; they favor platelet aggregation and leukocyte activation.
Nitric oxide (NO) represents the most important mediator of normal endothelial function: it exerts a powerful vasodilating and inhibitory action against platelet activation, the migration and proliferation of smooth muscle cells and the adhesion and activation of white blood cells. consequently, the reduced production of nitric oxide has been associated with vascular diseases such as atherosclerosis, diabetes or hyperlipidemia.
Beyond the intrinsic endocrine activity, we must not forget that the endothelium is itself the target of a multiplicity of neuro-hormonal signals. It also has mechanical "sensors" through which it constantly monitors the haemodynamic forces to which it is subjected. In response to these stimuli, the endothelial cells act accordingly by releasing vasoactive substances, whose balance (between vasodilating mediators and vasoconstrictors) maintains vascular homeostasis.
Endothelial dysfunction
The functionality of the endothelium is so important for the health of the whole organism that it has prompted researchers to coin the term "endothelial dysfunction";
The factors that can cause functional damage to the endothelium are numerous and for the most part are identified with cardiovascular risk factors (hypertension, hypercholesterolemia with an altered LDL / HDL ratio, diabetes, overweight, smoking, low-fiber diet and antioxidants, high-calorie diet rich in animal fats and / or simple sugars, sedentary life ...). It has been seen that subjects with these risk factors also have a reduced release of prostacyclin and nitric oxide, probably due to levels of free radicals, as opposed to the prevalence of pro-coagulating substances such as von Willebrand factor (vWf).
On the other hand, regular physical activity and a balanced diet rich in antioxidants are able to reduce cardiovascular risk and improve the health of the endothelium and blood vessels in general; not surprisingly, it has been seen and demonstrated that physical activity increases the bioavailability of nitric oxide and reduces the systemic inflammatory state. Smoking cessation, cholesterol control and the use of drugs that reduce insulin resistance in diabetics , blood pressure levels in hypertensive patients and hypercholesterolemia in patients with hyperlipidemia complete the picture of the most important measures to be adopted to reduce endothelial dysfunction.
